Peter van Mourik

62 Chapter 3 SUPPLEMENTARY DATA 0 3.125 6.25 12.5 25 50 100 200 0 700 1400 2100 2800 3500 [Genistein] ( µ M) DMSO VX-770 (3 µ M ) Additive 0 3.125 6.25 12.5 25 50 100 200 0 500 1000 1500 2000 2500 [Curcumin] ( µ M) DMSO Genistein (50 µ M ) Additive 0 3.125 6.25 12.5 25 50 100 200 0 500 1000 1500 2000 2500 [Curcumin] ( µ M) DMSO VX-770 (3 µ M ) Additive a b c F508del / S1251N (0.05 µ M forskolin) F508del / S1251N (0.05 µ M forskolin) F508del / S1251N (0.05 µ M forskolin) Organoid swelling (AUC t = 60 min) Organoid swelling (AUC t = 60 min) Organoid swelling (AUC t = 60 min) Supplementary figure S1. Dose-dependent potentiator synergy in F508del / S1251N organoids. (a-c) Forskolin-induced swelling of F508del / S1251N organoids stimulated with a dose range of genistein with or without VX-770 treatment (a), or stimulated with a dose range of curcumin with or without genistein (b) or VX-770 (c) at the indicated concentration of forskolin (this concentration was selected using Fig. 2f). The calculated additive responses of the single treatments are indicated as a dashed line. (a-c represent data averaged from 3 F508del / S1251N subjects. Each subject was measured at 2 to 5 independent culture time points in duplicate. Mean ± SD. The SD indicates the inter-subject variation).